The present invention relates to cerebral blood flow velocity monitoring system and method specifically a transcranial Doppler ultrasound device adapted for implantation into the human body, for detecting microembolic signals and changes in cerebral blood flow velocity and operatively connected to a drug delivery system.
Human implantable physiological and/or chemical sensors and/or implantable fluid delivery systems of various forms are used in present day clinical practice. U.S. Pat. No. 5,484,404 is an example of such a system and is incorporated herein by reference.
U.S. Pat. No. 5,188,106 describes an apparatus and method that provides for monitoring of heart contractility and blood flow output from the heart to control an implantable cardiac assist or therapy device to maintain cardiac output without invading the left heart or the arterial system of the patient. The ""106 patent is incorporated herein by reference.
While the ""106 patent describes a system in which the physiologic parameter of interest for hemodynamic control is the cardiac output, that is, the amount of blood flow from the heart per unit time, the required indicia for brain blood supply is determined by peripheral reactions influencing the resistance and capacitance of cerebral blood vessels. The hemodynamic differences between the cardiovascular and cerebrovascular systems are further illustrated by the applicability of the xe2x80x9cwindkesselxe2x80x9d model to the former as described in an article by Frank O. entitled xe2x80x9cDie Grundform des arteriellen pulses,xe2x80x9d published in Z Biol, vol. 37, pp. 483-526 (1899), but not to the latter, as argued in an article by Njemanze P. C. et al., entitled xe2x80x9cFourier analysis of the cerebrovascular system,xe2x80x9d published in Stroke, vol. 22, pp. 721-726 (1991). Furthermore, there appears to be distinct regulatory mechanisms of blood flow in the cerebrovascular system as compared to the cardiovascular system. Cerebrovascular autoregulation has been characterized using transcranial Doppler technique in an article by Aaslid R. et al., entitled xe2x80x9cAssessment of cerebral autoregulation dynamics from simultaneous arterial and venous transcranial Doppler recordings in humans,xe2x80x9d published in Stroke, vol. 22, pp. 1148-1154 (1991). The possibility that failure of cerebrovascular flow regulatory mechanisms such as in syncope may not be accompanied by fall in mean arterial blood pressure has been raised in an article by Njemanze P. C., entitled xe2x80x9cCerebral circulatory dysfunction and hemodynamic abnormalities in syncope during upright tilt test,xe2x80x9d published in Can J Cardiol, vol. 9, pp. 238-242 (1993). This work further emphasis the difference between cerebrovascular and cardiovascular systems thus requiring different monitoring approaches. Other publications by Njemanze P. C., entitled xe2x80x9cIsoproterenol induced cerebral hypoperfusion in a heart transplant recipient,xe2x80x9d published in PACE vol. 16, pp. 491-495 (1992) and another article by same author entitled xe2x80x9cCerebrovascular dysautoregulation syndrome in a heart-lung transplant recipient,xe2x80x9d published in J Cardiovascular Tech, vol. 10, pp. 227-232 (1992), suggest that cardiopulmonary reflexes may not be implicated in this mechanism. Even more importantly the changes in cerebral circulation may precede changes in cardiovascular system as suggested in a report by Njemanze P. C. entitled xe2x80x9cCerebrovascular dysautoregulation syndrome complexxe2x80x94brain hypoperfusion precedes hypotension and cardiac asystole,xe2x80x9d published in Jpn Circ J, vol. 58, pp. 293-297 (1994). It therefore follows that the ""106 patent may not be applicable to the cerebrovascular system. What is therefore desirable is a device that is responsive to blood flow changes detected in the cerebrovascular system in conditions such as stroke.
The annual incidence of stroke is approximately 700,000 per annum in the United States according to the statistics provided in a work by Broderick J., et al., entitled xe2x80x9cThe Greater Cincinnati/Northern Kentucky Stroke Study: preliminary first-ever and total incidence rates of stroke among blacks,xe2x80x9d published in Stroke, vol. 29, pp. 415-421 (1998). Ischemic strokes account for 80% of all stroke types. The high incidence and associated burden of disease of stroke have led to an interest to develop accurate predictors and prevention strategies. It is therefore desirable to have noninvasive techniques to identify surrogate markers of stroke events and their associated outcome. One such approach has been to utilize non-invasive cerebral blood flow velocity monitoring using transcranial Doppler ultrasound to measure microembolic signals also called high-intensity transient signals known to precede stroke events. Microembolic signals have been observed in patients with implanted mechanical and prosthetic devices and there are also spontaneously occurring microembolic signals in a variety of clinical conditions. Microembolic signals are identified by criteria set forth by the Consensus Committee of the Ninth International Cerebral Hemodynamic Symposium in a publication entitled xe2x80x9cBasic identification criteria of Doppler microembolic signals,xe2x80x9d published in Stroke, vol. 26, pp. 1123 (1995).
The occurrence of microembolic signals has been recorded during open-heart surgery, carotid endarterectomy and in patients with prosthetic heart valves, ventricular assist devices and those with atrial fibrillation. The association of microembolic signals with neurological and neuropsychological deficits in patients after open-heart surgery has been described in an article by Clark R. E., et al., entitled xe2x80x9cMicroemboli during coronary artery bypass grafting genesis and effects on outcome,xe2x80x9d published in J Thorac Cardiovasc Surg, vol. 109, pp. 249-258 (1995).
Spencer M. in an article entitled xe2x80x9cTranscranial Doppler monitoring and causes of stroke from carotid endarterectomy,xe2x80x9d published in Stroke, vol. 28, pp. 685-691 (1997), ascribed postoperative cerebral ischemia in patients with carotid endarterectomy to the high rates of microembolic signals during surgery and in the immediate postoperative period. The enormity and severity of the problem of symptomatic and asymptomatic microemboli remains to be fully elucidated.
One object of the present invention is to use it in conjunction with ventricular assist devices. Considering that while tens of thousands of United States patients need a donor heart each year, only about 2,000 receive one. The ventricular assist devices have been shown to add months, even years, to patients"" lives while the wait for donor heart to become available. Close to three thousand patients have received ventricular assist devices in Europe and America. One major limitation of the ventricular assist devices is the occurrences of clinical thromboembolism in up to 30%, dependent on device type and implantation center. Wagner W. R., and Johnson P. C., in an article entitled xe2x80x9cTherapeutic techniques for reducing thrombosis after cardiovascular implants, published in a book by Klizman B., (ed.) entitled xe2x80x9cProblems in General Surgeryxe2x80x9d, published by JB Lippincott Co., Philadelphia, Pa.: chapter 11, pp. 241-246 (1994), have suggested that thromboembolism remains a significant impediment to the choice application of ventricular assist devices. However, they demonstrated prolonged life of the patients with cardiomyopathy using ventricular assist devices until heart transplantation, which makes identification and prevention of thromboembolism an important strategy in patient care for prevention of strokes in this population. Wilhelm C. R., et al., in an article entitled xe2x80x9cMeasurement of hemostatic indexes in conjunction with transcranial Doppler sonography in patients with ventricular assist devices,xe2x80x9d published in Stroke vol. 30, pp. 2554-2561 (1999), have demonstrated that microembolic signals identified using transcranial Doppler are related to increased hemostatic activity in patients with ventricular assist devices. Ventricular assist devices of different designs are now in clinical use. Left ventricular assist device (Novacor Left Ventricular Assist Systemxe2x80x94Baxter Healthcare, Deerfield, Ill.) and bi-ventricular assist device (Thoratec(copyright) VAD system) are offered commercially for implantation in patients. Measures to reduce thrombus formation include the use of Thoralon(copyright), (Thoratec(copyright)) a patented thromboresistant and biocompatible material with thromboresistant properties. However, significant microembolic signals still persist. An evaluation of the thromboembolic events was carried out in a recent article by Wilhelm C. R., et al., entitled xe2x80x9cMeasurement of hemostatic indexes in conjunction with transcranial Doppler Sonography in patients with ventricular assist devices,xe2x80x9d published in Stroke vol. 30, pp. 2554-2561 (1999). The authors classified thromboembolic events as transient ischemic attacks (symptoms resolving within 24 hours) or cerebrovascular accidents (permanent deficit or symptom duration  greater than 24 hours). Thirteen thromboembolic events, including five cerebrovascular accidents and eight transient ischemic attacks, were recorded in 12 (44%) of the 27 patients (of which 21 were males and 6 were females). For all patients, microembolic signals were not observed in any transcranial Doppler measurements prior to implantation. Temporally, seven of the events occurred within the first four weeks after implantation. Of the twelve patients with Novacor left ventricular assist devices, one half had microembolic signals detected compared with 100% of the patients with Thoratec(copyright) ventricular assist devices (p=0.0001 vs Novacor) and 100% of patients with Thoratec(copyright) BiVADs (p=0.014 vs Novacor). The generation of thrombin in vivo was related in a highly significant manner to the presence of microembolic signals showering in patients with ventricular assist devices. All patients were on anticoagulation regimen. The results of this study showed that it would be desirable to have a system that may diagnose and prevent thromboembolus in patients with ventricular assist devices. The present invention accomplishes a continual detection of microembolic signals and provides countermeasures to prevent neurological deficits.
Another clinically related use of the present invention is in patients with atrial fibrillation. Atrial fibrillation causes stasis of blood flow in the left atrial appendage, leading to thrombus formation and embolic stroke. Although, atrial fibrillation is associated with a six-fold increased risk of stroke, most patients with atrial fibrillation never suffer stroke, however, those with increased microembolic signals are most likely to suffer strokes. It is therefore desirable to continually detect microembolic signals and initiate countermeasures to prevent thromboembolus.
Another clinical use of the present invention relates to patients with carotid artery stenosis. It has been reported that the frequency of microembolic signals in patients with atrial fibrillation appears to be lower than that found in carotid artery stenosis as has been reported by Cullinane M., et al., in an article entitled xe2x80x9cAsymptomatic embolization in subjects with atrial fibrillation not taking anticoagulants: a prospective study,xe2x80x9d published in Stroke, vol. 29, pp. 1810-1815 (1998). Similarly, patients with aortic arch atheroma are also expected to have increased microembolic signals and may benefit from use of the present invention.
A further object of the present invention is its use in patients with prosthetic heart valves. Prosthetic heart valves may be associated with formation of thrombus and thromboembolism. Thrombus and thromboembolism are known complications of mechanical heart valves and can result in serious neurological deficits or death. Certain measures in the design of new prosthetic valves have been undertaken to reduce the danger of thromboembolus. Georgiadis D., et al., in an article titled xe2x80x9cTranscranial Doppler detection of microemboli in prosthetic heart valve patients: dependency upon valve type,xe2x80x9d published in Eur J Cardiothoracic Surg, vol. 10, pp. 253-258 (1996), described asymptomatic microembolic signals in patients with prosthetic heart valves. To prevent these complications a common treatment involves life-long anticoagulant therapy. However, continuous anticoagulant therapy itself leads to increased risk of anticoagulant-related hemorrhage. It is therefore desirable to have timely detection of the microembolic signals and target the use of the anticoagulant therapy only when the microembolic signals occur. This approach is accomplished with the present invention.
Similarly, prosthetic vascular grafts and stent devices are becoming more common for clinical applications. Various rigid stent devices have been utilized to hold and support bioprosthetic implants, such as heart valves. Similarly, intracranial stent devices have been described. Theron J. G., et al., in an article entitled xe2x80x9cCarotid artery stenosis: treatment with protected balloon angioplasty and stent placement,xe2x80x9d published in Radiology, vol. 201, pp. 627-636 (1996), described the carotid angioplasty and stent placement as an alternative to carotid endarterectomy for treatment of carotid stenosis. Common to all these devices are thromboembolic complications known to result from turbulent blood flow through vascular grafts. This has been associated with abrupt variations in the diameter of the blood vessel lumen, as may result from improper size matching of the vascular implant graft. The early detection and remedy of severe thromboembolic complications as a result of vascular implant grafts and stents are objects of the present invention.
Yet another object of the present invention is to prevent stroke in high-risk group of patients. For example, a patient who has suffered a transient ischemic attack is thirteen times at greater risk of suffering a stroke. This risk further increases if the patient is elderly, hypertensive, with  greater than 70% carotid stenosis, diabetic, smokes and has coronary heart disease. Prevention of stroke in this group of patients is feasible using the device described in this disclosure.
Patients with stroke may benefit from early thrombolytic therapy within 3 hours of onset of symptoms as described in the protocol by the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group, entitled xe2x80x9cTissue plasminogen activator for acute ischemic stroke,xe2x80x9d published in N Engl J Med, vol. 333, pp. 1581-1587 (1995). However, crucial time is lost between clinical detection of the thromboembolic event and administration of this life-saving thrombolytic therapy. By use of the present invention implanted in a patient at risk of stroke, detection of thromboembolus is within seconds and initiation of thrombolytic therapy could be immediate, so that, time is gained and life saved. Moreover, it has been hypothesized in an article by Alexandrov A. V., et al., entitled xe2x80x9cHigh rate of complete recanalization and dramatic clinical recovery during tPA infusion when continuously monitored with 2-MHz time in the future preclude the use of implanted electrodes for EEG recordings and subsequent epilepsy surgery on the temporal lobe in this category of patients. Preliminary findings by Njemanze P. C., et al., disclosed in an article entitled xe2x80x9cCerebral blood flow velocity and EEG amplitude in generalized seizures: a case study,xe2x80x9d published in J Neuroimag, vol. 2, pp. 151-155 (1992) have shown that marked cerebral blood flow velocity increases associated with onset of seizure activity could be detected within seconds before onset of clinical manifestation. The present invention provides means that would allow for injection of anti-epileptic medication to remedy the seizures before clinical onset and is particularly of essence in patients prone to have xe2x80x98status epilepticusxe2x80x99. Drugs like diazepam and newer fast-acting anti-epileptic drugs could be injected via internal or external drug delivery systems telemetrically responsive to the implanted transcranial Doppler ultrasound device in seizure patients.
Similarly, the present invention could be applied to patients requiring defibrillation. In an article by Njemanze P. C., entitled xe2x80x9cCerebrovascular dysautoregulation syndrome complexxe2x80x94brain hypoperfusion precedes hypotension and cardiac asystole,xe2x80x9d published in Jpn Circ J, vol. 58, pp. 293-297 (1994), the drop in cerebral blood flow velocity was shown to precede cardiac asystole by as much as two minutes. It is therefore desirable to gain time by telemetrically synchronizing the function of the implanted transcranial Doppler ultrasound device and the defibrillator. Commercially available implanted defibrillators from several vendors such as Medtronic Inc. Minneapolis, Minn. or external defibrillators for example Model HP S01/E01/EM01 Heartstream ForeRunner AED by Healthcare, Agilent (Hewlett Packard subsidiary located at Andover Mass.) could be adapted for this application in patients prone to severe arrhythmia.
Another object of the present invention is monitoring of patients with obstructive sleep apnea. Diomedi M., et al., in an article entitled xe2x80x9cCerebral hemodynamic changes in sleep apnea syndrome and continuous positive airway pressure treatment,xe2x80x9d published in Neurology, vol. 51, pp. 1051-1056 (1998), have suggested that snoring and sleep apnea are associated with increased risk of stroke and attributed this to diminished cerebral vasodilator reserve. The latter was studied using transcranial Doppler technique. Presently, available techniques for delivering airway flow use the patient""s snoring to adjust the pressure settings. However, changes in cerebral blood flow velocity precede these other variables. It is therefore desirable to have long-term monitoring of cerebral blood flow velocity in conjunction with oximetry as a means for regulating nasal continuous positive airway pressure in patients with sleep apnea. The system of the present invention could be programmed to sound an audible alarm to patients with sleep apnea at the appropriate time. Several oximetry devices are available from a number of vendors such as Mallinckrodt at Tucson, Ariz. The present invention using cerebral blood flow velocity in conjunction with indicia of oximetry could telemetrically regulate the nasal continuous positive airway pressure delivered from a device such as Solo(copyright) Plus LX CPAP system obtainable from Respironics(copyright), a company in Pittsburgh, Pa.
A further object of the present invention is to use the measured cerebral blood flow velocity to perform a workload assessment. The matching of cerebral blood flow velocity levels to increased psycho-physiologic workload in the rehabilitation phase after stroke could be performed in a more structured manner using the present invention.
The present invention overcomes some or all of the shortcomings of the prior art by early detection of microembolic signals and cerebral blood flow velocity monitoring using a transcranial Doppler ultrasound device adapted for implantation into the human body and an external handheld computer.
Additionally, there is provided an automatic triggering of the computer-programmed function of an infusion pump to inject a thrombolytic agent (for example tissue plasminogen activator (rt-PA), heparin, etc) into the vein (or artery) of the patient. Combined intravenous and intra-arterial rt-PA has been studied by Lewandowski C. A., et al., disclosed in an article entitled xe2x80x9cCombined intravenous and intra-arterial rt-PA versus intra-arterial therapy of acute ischemic stroke: emergency management of stroke (EMS) bridging trial,xe2x80x9d published in Stroke, vol. 30, pp. 2598-2605 (1999). Information about a thrombolytic agent rt-PA is provided in the xe2x80x9cPhysiciansxe2x80x9d desk reference,xe2x80x9d 53 edition, Medical Economics Company, Montvale, N.J.: pp. 1057-1061 (1999), under a trade-name Activase(copyright) (generic name Altepase recombinant) produced by recombinant DNA technology by Genentech Inc., a company in San Francisco, Calif.
The special embodiment of this invention is illustrated in the specification, it includes block and schematic diagrams for the format of the instrumentation, and how the system functions is shown by way of example. The human involved will be referred to as xe2x80x9cpatientxe2x80x9d by way of example. The system comprises a transcranial Doppler ultrasound device adapted for implantation in the human body, oximeter, external handheld computer, and an implantable mini-drug delivery system or external drug infusion system. The present invention may use conventional transcranial Doppler pulsed wave 2 MHz ultrasound transducer, however, the continuous wave mode could in principle be applied. Multi-gate Doppler sampling covering a range of depths will provide even better access to cerebral vessels and is a preferred option. These and other modifications will appear obvious to anybody skilled in the art. The implantable transcranial Doppler ultrasound device comprises a transducer placed on the acoustic window of the temporal bone above the zygomatic arc and focused on the middle cerebral arteries unilaterally (or bilaterally) by way of example, a voltage generator and gate, a receiver and gate, microprocessor that executes the programs such as spectral analysis and sending the information to the external handheld computer via a radio-frequency (RF) transmitter/receiver. The unit detects the respiratory status using measurement of oxygen saturation of hemoglobin. The entire unit is powered using long battery life such as lithium battery similar to that used for implanted pacemakers. Low modulus Tixe2x80x94Nbxe2x80x94Zr alloys could be used for fabrication material for the implanted parts to provide enhanced biocompatibility and hemocompatibility. Furthermore, at least one surface of the implantable device could be covered with rt-PA to avoid inflammatory reactions of the body and formation of fibrous capsules, which ordinarily occur after implantation.
The external base unit comprises a handheld computer with an attached RF transmitter/receiver and antenna, a central processing unit (included in a microcomputer), a loudspeaker, a monitor for spectral display, a keyboard, a global positioning system and communication access to the Internet. Several modifications of the handheld computer could be used for the purpose of this invention including integration of the features in a cellular telephone or use of a handheld computer device such as Visor(trademark) Platinum from Handspring Inc. Mountainview, Calif. Other features such as voice-activated controls, global positioning (GPS) module, full Internet access and high speed modem already available in commercial handheld computers and could well be incorporated into the present invention for easy use.
The internally implanted drug delivery pump could be physically connected to the implanted transcranial Doppler ultrasound device or made telemetrically responsive. The drug delivery system could comprise several compartments of the drug reservoir, with the pump responsive to signals from the transcranial Doppler ultrasound device to regulate release of the needed medication via a catheter grafted into the vein (or artery), to infuse the medication in a similar manner as disclosed in U.S. Pat. No. 5,484,404 by Schulman et al. The several compartments of the drug reservoir could be used to store medication that is externally introduced by percutaneous injection under X-ray control. Rt-PA for example, could be synthesized using the complementary DNA (cDNA) for natural human tissue-type plasminogen activator obtained from a melanoma cell line. Improvements in genetic and technical procedures of the present manufacturing process could make it possible to produce the rt-PA within micro-compartments, and creating an internal drug reservoir that would preclude external refill of the medication.
The external drug delivery system comprises a programmable pump, a radio frequency receiver, intravenous cannula and syringe/reservoir containing the thrombolytic agent. There is provided a communication means between the implanted transcranial Doppler ultrasound device and the external drug delivery system.
In order to use the system, the patient could enter relevant information such as subjective symptoms into the handheld computer and send the information to the attending physician via the Internet. The attending physician using his/her physician""s transcranial Doppler monitoring,xe2x80x9d published in Stroke, vol. 31, pp. 610-614 (2000), that continuous ultrasonic energy transmission focused on clot location by transcranial Doppler monitoring may expose clot surface to action of tPA. This supports earlier report by Lauer C. G., et al., entitled xe2x80x9cEffect of ultrasound on tissue-type plasminogen activator thrombolysis,xe2x80x9d published in Circulation, vol. 86, 1257-1264 (1992).
Yet another application of the present invention can be seen when one reviews the current use of neuroprotective agents in clinical trials. The use of the neuroprotective agents of the class N-methyl-D-aspartate (NMDA) antagonists was based on the finding that an ischemic brain injury produces elevated levels of the excitatory neurotransmitter glutamate, which leads to excessive stimulation of the NMDA receptor as described in an article by Lees K. R., entitled xe2x80x9cCerestat and other NMDA antagonists in ischemic stroke,xe2x80x9d published in Neurology, vol. 49, pp. S66-S69 (1997). The use of potentially effective neuroprotective agents such as NMDA antagonists has particular appeal in acute stroke, because these compounds are not associated with an increased risk of hemorrhage and could therefore be administered without a screening brain imaging (CT scan or MRI). The precise time window to administer neuroprotective agents is not known. Animal studies demonstrate effectiveness when NMDA antagonists are administered minutes after an infarction as demonstrated in a work by Simon R, and Shiraishi K., entitled xe2x80x9cN-methyl-D-aspartate antagonist reduces stroke size and regional glucose metabolism,xe2x80x9d published in the Annals of Neurology, vol. 27, pp. 606-611 (1990). It is therefore desirable to have a means to detect an acute stroke event seconds to minutes after onset and trigger the administration of a neuroprotective agent. This precise goal can be accomplished with use of the present invention.
Yet another object of the present invention is the use of combined acute therapies in stroke. Recent experimental evidence obtained in the work by Heiss W. D., et al., entitled xe2x80x9cWhich targets are relevant for therapy of acute stroke?,xe2x80x9d published in Stroke, vol. 30, pp. 1468-1489 (1999), suggests a beneficial effect of the use of the neuroprotective agents concomitantly with reperfusion therapy. Grotta J. C. in an article entitled xe2x80x9cAcute stroke therapy at the millennium: consummating the marriage between the laboratory and bedside: the Feinberg Lecture,xe2x80x9d published in Stroke, vol. 30, pp. 1722-1728 (1999), suggested combinations of thrombolytic and neuroprotective therapies. One of the benefits is that neuroprotective drugs may extend the therapeutic window for thrombolysis. Secondly, thrombolysis which promotes acute reperfusion, is likely to facilitate higher concentrations of neuroprotective agent in the critically under perfused penumbral region. It is therefore desirable to have a non-invasive technique that will detect acute stroke events and trigger the administration of neuroprotective as well as thrombolytic agents. The clinical trial in acute stroke using neuroprotective agent Selfotel (Avantis) yielded disappointing results when administration was delayed usually within three to six hours after stroke, as described in the protocol of a report by Davis S. M., et al., entitled xe2x80x9cSelfotel in acute ischemic stroke. Possible neurotoxic effects of an NMDA antagonist,xe2x80x9d published in Stroke, vol. 30, pp. 347-345 (2000). The authors ascribe some of the blame to the poor choice of time windows for neuroprotective strategies. This problem is overcome by use of the present invention.
Yet another object of the present invention is the synchronization of function of the transcranial Doppler ultrasound device with other implanted mechanical devices and external physiologic assist devices. The function of a pacemaker could be synchronized with that of the implanted transcranial Doppler ultrasound device, for example, cerebral blood flow velocity reduction during pacing could automatically trigger a functional mode of a pacemaker to maintain cerebral perfusion in a feedback loop, thereby preventing pacemaker syndrome. Njemanze P. C., in an article entitled xe2x80x9cCerebral circulatory changes in a case of pacemaker syndrome,xe2x80x9d published in J Cardiovasc Technol, vol. 11, pp. 105-109 (1993), described a case where the function of the pacemaker was associated with reduction of cerebral blood flow velocity. Predisposition to syncope could be assessed using threshold values established for syncope as described in an article by Njemanze P. C., entitled xe2x80x9cCritical limits of pressure flow relation in the human brain,xe2x80x9d published in Stroke, vol. 23, pp. 1743-1747 (1992). The function of the pacemaker could be regulated by telemetric communication between the present invention and the implanted pacemaker.
A further advantage of this invention is that it will allow for event-related monitoring of the cerebral blood flow velocity in seizure disorders. During seizures there could be a brief period of cessation of blood flow to the brain. This was disclosed in an article by Njemanze P. C., et al., entitled xe2x80x9cCerebral blood flow velocity and EEG amplitude in generalized seizures: a case study,xe2x80x9d published in J Neuroimag, vol. 2, pp. 151-155 (1992). This may influence mortality and morbidity in intractable seizure disorders. It is therefore desirable to have a system that documents the state of cerebral blood flow velocity measurements during seizure activity. This could be synchronized with simultaneously recording of video electroencephalography. The present invention allows for detection and long-term monitoring of seizure events especially in cases of intractable seizures. This approach will provide therapeutic measures and may at some identification number and access password could carry out review of the technical parameters of the implanted transcranial Doppler ultrasound device including serial number of the device, lot number, power source status and self-test diagnostic programs via the Internet. The attending physician could alter the program of the pump such a bolus dose, functional regulation of the transcranial Doppler signals including depth, artifact exclusion criteria, and even review current files of microembolic signal rate before and after each drug delivery regimen. The authorization for the physician to alter the functionality of the system is subject to drug prescription guidelines. Restricted Internet access via specified websites ensure strict compliance with the ethical codes implicated in the patient care services.
Another feature of the present invention provides a communication means to alert the emergency medical service team by automatically dialing the service via phone line or wireless connection in the event of a stroke. The handheld computer reads the coordinates of the location of the patient within a town from an incorporated global positioning system device. Such global positioning system devices are available from a number of vendors such as Magnavox, a company in Torrance, Calif. The system provides means for the patient to override any false-positive calls at initiation.
The transcranial Doppler ultrasound device could be adapted for implantation on one side of the body to monitor unilateral carotid artery system considering that stroke will occur at a higher frequency on the side with greater carotid plaque lesion. The asymmetric occurrence of carotid plaque lesions in the carotid systems has been related to handedness as described in an article by Njemanze P. C., entitled xe2x80x9cHandedness and carotid plaque lesionxe2x80x9d published in Stroke, vol. 23, pp. 1679-1680 (1992) and a related article by same author entitled xe2x80x9cCarotid stenosis determines impairment of ipsilateral dexterity in stroke,xe2x80x9d published in Stroke, vol. 31, pp. 545-546 (2000). It is therefore of essence to perform noninvasive carotid color flow Doppler imaging studies to determine plaque lesion size, plaque morphology including ulcerations, and likely plaque composition. The choice of the side for the implant would be based on the side with greater clinical and B-mode ultrasound risk for microembolic signals and the rate of detection of microembolic signals by conventional transcranial Doppler monitoring of the ipsilateral carotid system. However, bilateral implantations focusing on two vessels (for example, left and right middle cerebral arteries or internal carotid arteries) are feasible using bilateral transcranial Doppler ultrasound device with two ultrasound probes. It may be possible to have left and/or right detection trigger pump release of the thrombolytic agent. Bilateral implantations may be necessitated if there are separate risk factors in two vascular territories for example in the anterior versus posterior cerebral circulation.